Long-acting β2-agonist monotherapy vs continued therapy with inhaled corticosteroids in patients with persistent asthma

A randomized controlled trial

Stephen C. Lazarus, Homer A. Boushey, John V. Fahy, Vernon Chinchilli, Robert F. Lemanske, Christine A. Sorkness, Monica Kraft, James E. Fish, Stephen P. Peters, Timothy Craig, Jeffrey M. Drazen, Jean G. Ford, Elliot Israel, Richard J. Martin, Elizabeth A. Mauger, Sami A. Nachman, Joseph D. Spahn, Stanley J. Szefler

Research output: Contribution to journalArticle

325 Citations (Scopus)

Abstract

Context: Long-acting β2-agonists are prescribed for patients with persistent asthma and are sometimes used without inhaled corticosteroids (ICSs). No evidence exists, however, to support their use as monotherapy in adults with persistent asthma. Objective: To examine the effectiveness of salmeterol xinafoate, a long-acting β2-agonist, as replacement therapy in patients whose asthma is well controlled by low-dose triamcinolone acetonide, an ICS. Design and Setting: A 28-week, randomized, blinded, placebo-controlled, parallel group trial conducted at 6 National Institutes of Health-sponsored, university-based ambulatory care centers from February 1997 to January 1999. Participants: One hundred sixty-four patients aged 12 through 65 years with persistent asthma that was well controlled during a 6-week run-in period of treatment with inhaled triamcinolone (400 μg twice per day). Interventions: Patients were randomly assigned to continue triamcinolone therapy (400 μg twice per day; n=54) or switch to salmeterol (42 μg twice per day; n=54) or to placebo (n=56) for 16 weeks, after which all patients received placebo for an additional 6-week run-out period. Main Outcome Measures: Change in morning and evening peak expiratory flow (PEF), forced expiratory volume in 1 second (FEV1), self-assessed asthma symptom scores, rescue albuterol use, asthma-specific quality-of-life scores, treatment failure, asthma exacerbation, bronchial reactivity, and markers of airway inflammation, compared among the 3 treatment groups. Results: During the 16-week randomized treatment period, no significant differences between the salmeterol and triamcinolone groups were observed for conventional outcomes of clinical studies of asthma therapy-morning PEF, evening PEF, asthma symptom scores, rescue albuterol sulfate use, or quality of life. Both active treatments were superior to placebo. However, the salmeterol group had more treatment failures than the triamcinolone group (13/54 [24%] vs 3/54 [6%]; P=.004), as well as more asthma exacerbations (11/54 [20%] vs 4/54 [7%]; P=.04), greater increases in median (interquartile range) sputum eosinophils (2.4% [0.0% to 10.6%] vs -0.1% [-0.7% to 0.3%]; P<.001), eosinophil cationic protein (71 [-2 to 430] U/L vs -4 [-31 to 56] U/L; P=.005), and tryptase (3.1 [2.1 to 7.6] ng/mL vs 0.0 [0.0 to 0.7] ng/mL; P<.001). The duration of benefit when patients were switched from active treatment to placebo after 22 weeks of randomized treatment was not significantly longer in the triamcinolone group than in the salmeterol group. Conclusions: Patients with persistent asthma well controlled by low doses of triamcinolone cannot be switched to salmeterol monotherapy without risk of clinically significant loss of asthma control.

Original languageEnglish (US)
Pages (from-to)2583-2593
Number of pages11
JournalJournal of the American Medical Association
Volume285
Issue number20
StatePublished - May 23 2001

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Adrenal Cortex Hormones
Asthma
Randomized Controlled Trials
Triamcinolone
Placebos
Therapeutics
Albuterol
Treatment Failure
Quality of Life
Outcome Assessment (Health Care)
Eosinophil Cationic Protein
Tryptases
Triamcinolone Acetonide
Forced Expiratory Volume
National Institutes of Health (U.S.)
Ambulatory Care
Sputum
Eosinophils
Salmeterol Xinafoate
Inflammation

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Lazarus, Stephen C. ; Boushey, Homer A. ; Fahy, John V. ; Chinchilli, Vernon ; Lemanske, Robert F. ; Sorkness, Christine A. ; Kraft, Monica ; Fish, James E. ; Peters, Stephen P. ; Craig, Timothy ; Drazen, Jeffrey M. ; Ford, Jean G. ; Israel, Elliot ; Martin, Richard J. ; Mauger, Elizabeth A. ; Nachman, Sami A. ; Spahn, Joseph D. ; Szefler, Stanley J. / Long-acting β2-agonist monotherapy vs continued therapy with inhaled corticosteroids in patients with persistent asthma : A randomized controlled trial. In: Journal of the American Medical Association. 2001 ; Vol. 285, No. 20. pp. 2583-2593.
@article{69bd26c0bcb849b481ec5ba22dc16abe,
title = "Long-acting β2-agonist monotherapy vs continued therapy with inhaled corticosteroids in patients with persistent asthma: A randomized controlled trial",
abstract = "Context: Long-acting β2-agonists are prescribed for patients with persistent asthma and are sometimes used without inhaled corticosteroids (ICSs). No evidence exists, however, to support their use as monotherapy in adults with persistent asthma. Objective: To examine the effectiveness of salmeterol xinafoate, a long-acting β2-agonist, as replacement therapy in patients whose asthma is well controlled by low-dose triamcinolone acetonide, an ICS. Design and Setting: A 28-week, randomized, blinded, placebo-controlled, parallel group trial conducted at 6 National Institutes of Health-sponsored, university-based ambulatory care centers from February 1997 to January 1999. Participants: One hundred sixty-four patients aged 12 through 65 years with persistent asthma that was well controlled during a 6-week run-in period of treatment with inhaled triamcinolone (400 μg twice per day). Interventions: Patients were randomly assigned to continue triamcinolone therapy (400 μg twice per day; n=54) or switch to salmeterol (42 μg twice per day; n=54) or to placebo (n=56) for 16 weeks, after which all patients received placebo for an additional 6-week run-out period. Main Outcome Measures: Change in morning and evening peak expiratory flow (PEF), forced expiratory volume in 1 second (FEV1), self-assessed asthma symptom scores, rescue albuterol use, asthma-specific quality-of-life scores, treatment failure, asthma exacerbation, bronchial reactivity, and markers of airway inflammation, compared among the 3 treatment groups. Results: During the 16-week randomized treatment period, no significant differences between the salmeterol and triamcinolone groups were observed for conventional outcomes of clinical studies of asthma therapy-morning PEF, evening PEF, asthma symptom scores, rescue albuterol sulfate use, or quality of life. Both active treatments were superior to placebo. However, the salmeterol group had more treatment failures than the triamcinolone group (13/54 [24{\%}] vs 3/54 [6{\%}]; P=.004), as well as more asthma exacerbations (11/54 [20{\%}] vs 4/54 [7{\%}]; P=.04), greater increases in median (interquartile range) sputum eosinophils (2.4{\%} [0.0{\%} to 10.6{\%}] vs -0.1{\%} [-0.7{\%} to 0.3{\%}]; P<.001), eosinophil cationic protein (71 [-2 to 430] U/L vs -4 [-31 to 56] U/L; P=.005), and tryptase (3.1 [2.1 to 7.6] ng/mL vs 0.0 [0.0 to 0.7] ng/mL; P<.001). The duration of benefit when patients were switched from active treatment to placebo after 22 weeks of randomized treatment was not significantly longer in the triamcinolone group than in the salmeterol group. Conclusions: Patients with persistent asthma well controlled by low doses of triamcinolone cannot be switched to salmeterol monotherapy without risk of clinically significant loss of asthma control.",
author = "Lazarus, {Stephen C.} and Boushey, {Homer A.} and Fahy, {John V.} and Vernon Chinchilli and Lemanske, {Robert F.} and Sorkness, {Christine A.} and Monica Kraft and Fish, {James E.} and Peters, {Stephen P.} and Timothy Craig and Drazen, {Jeffrey M.} and Ford, {Jean G.} and Elliot Israel and Martin, {Richard J.} and Mauger, {Elizabeth A.} and Nachman, {Sami A.} and Spahn, {Joseph D.} and Szefler, {Stanley J.}",
year = "2001",
month = "5",
day = "23",
language = "English (US)",
volume = "285",
pages = "2583--2593",
journal = "JAMA - Journal of the American Medical Association",
issn = "0002-9955",
publisher = "American Medical Association",
number = "20",

}

Lazarus, SC, Boushey, HA, Fahy, JV, Chinchilli, V, Lemanske, RF, Sorkness, CA, Kraft, M, Fish, JE, Peters, SP, Craig, T, Drazen, JM, Ford, JG, Israel, E, Martin, RJ, Mauger, EA, Nachman, SA, Spahn, JD & Szefler, SJ 2001, 'Long-acting β2-agonist monotherapy vs continued therapy with inhaled corticosteroids in patients with persistent asthma: A randomized controlled trial', Journal of the American Medical Association, vol. 285, no. 20, pp. 2583-2593.

Long-acting β2-agonist monotherapy vs continued therapy with inhaled corticosteroids in patients with persistent asthma : A randomized controlled trial. / Lazarus, Stephen C.; Boushey, Homer A.; Fahy, John V.; Chinchilli, Vernon; Lemanske, Robert F.; Sorkness, Christine A.; Kraft, Monica; Fish, James E.; Peters, Stephen P.; Craig, Timothy; Drazen, Jeffrey M.; Ford, Jean G.; Israel, Elliot; Martin, Richard J.; Mauger, Elizabeth A.; Nachman, Sami A.; Spahn, Joseph D.; Szefler, Stanley J.

In: Journal of the American Medical Association, Vol. 285, No. 20, 23.05.2001, p. 2583-2593.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Long-acting β2-agonist monotherapy vs continued therapy with inhaled corticosteroids in patients with persistent asthma

T2 - A randomized controlled trial

AU - Lazarus, Stephen C.

AU - Boushey, Homer A.

AU - Fahy, John V.

AU - Chinchilli, Vernon

AU - Lemanske, Robert F.

AU - Sorkness, Christine A.

AU - Kraft, Monica

AU - Fish, James E.

AU - Peters, Stephen P.

AU - Craig, Timothy

AU - Drazen, Jeffrey M.

AU - Ford, Jean G.

AU - Israel, Elliot

AU - Martin, Richard J.

AU - Mauger, Elizabeth A.

AU - Nachman, Sami A.

AU - Spahn, Joseph D.

AU - Szefler, Stanley J.

PY - 2001/5/23

Y1 - 2001/5/23

N2 - Context: Long-acting β2-agonists are prescribed for patients with persistent asthma and are sometimes used without inhaled corticosteroids (ICSs). No evidence exists, however, to support their use as monotherapy in adults with persistent asthma. Objective: To examine the effectiveness of salmeterol xinafoate, a long-acting β2-agonist, as replacement therapy in patients whose asthma is well controlled by low-dose triamcinolone acetonide, an ICS. Design and Setting: A 28-week, randomized, blinded, placebo-controlled, parallel group trial conducted at 6 National Institutes of Health-sponsored, university-based ambulatory care centers from February 1997 to January 1999. Participants: One hundred sixty-four patients aged 12 through 65 years with persistent asthma that was well controlled during a 6-week run-in period of treatment with inhaled triamcinolone (400 μg twice per day). Interventions: Patients were randomly assigned to continue triamcinolone therapy (400 μg twice per day; n=54) or switch to salmeterol (42 μg twice per day; n=54) or to placebo (n=56) for 16 weeks, after which all patients received placebo for an additional 6-week run-out period. Main Outcome Measures: Change in morning and evening peak expiratory flow (PEF), forced expiratory volume in 1 second (FEV1), self-assessed asthma symptom scores, rescue albuterol use, asthma-specific quality-of-life scores, treatment failure, asthma exacerbation, bronchial reactivity, and markers of airway inflammation, compared among the 3 treatment groups. Results: During the 16-week randomized treatment period, no significant differences between the salmeterol and triamcinolone groups were observed for conventional outcomes of clinical studies of asthma therapy-morning PEF, evening PEF, asthma symptom scores, rescue albuterol sulfate use, or quality of life. Both active treatments were superior to placebo. However, the salmeterol group had more treatment failures than the triamcinolone group (13/54 [24%] vs 3/54 [6%]; P=.004), as well as more asthma exacerbations (11/54 [20%] vs 4/54 [7%]; P=.04), greater increases in median (interquartile range) sputum eosinophils (2.4% [0.0% to 10.6%] vs -0.1% [-0.7% to 0.3%]; P<.001), eosinophil cationic protein (71 [-2 to 430] U/L vs -4 [-31 to 56] U/L; P=.005), and tryptase (3.1 [2.1 to 7.6] ng/mL vs 0.0 [0.0 to 0.7] ng/mL; P<.001). The duration of benefit when patients were switched from active treatment to placebo after 22 weeks of randomized treatment was not significantly longer in the triamcinolone group than in the salmeterol group. Conclusions: Patients with persistent asthma well controlled by low doses of triamcinolone cannot be switched to salmeterol monotherapy without risk of clinically significant loss of asthma control.

AB - Context: Long-acting β2-agonists are prescribed for patients with persistent asthma and are sometimes used without inhaled corticosteroids (ICSs). No evidence exists, however, to support their use as monotherapy in adults with persistent asthma. Objective: To examine the effectiveness of salmeterol xinafoate, a long-acting β2-agonist, as replacement therapy in patients whose asthma is well controlled by low-dose triamcinolone acetonide, an ICS. Design and Setting: A 28-week, randomized, blinded, placebo-controlled, parallel group trial conducted at 6 National Institutes of Health-sponsored, university-based ambulatory care centers from February 1997 to January 1999. Participants: One hundred sixty-four patients aged 12 through 65 years with persistent asthma that was well controlled during a 6-week run-in period of treatment with inhaled triamcinolone (400 μg twice per day). Interventions: Patients were randomly assigned to continue triamcinolone therapy (400 μg twice per day; n=54) or switch to salmeterol (42 μg twice per day; n=54) or to placebo (n=56) for 16 weeks, after which all patients received placebo for an additional 6-week run-out period. Main Outcome Measures: Change in morning and evening peak expiratory flow (PEF), forced expiratory volume in 1 second (FEV1), self-assessed asthma symptom scores, rescue albuterol use, asthma-specific quality-of-life scores, treatment failure, asthma exacerbation, bronchial reactivity, and markers of airway inflammation, compared among the 3 treatment groups. Results: During the 16-week randomized treatment period, no significant differences between the salmeterol and triamcinolone groups were observed for conventional outcomes of clinical studies of asthma therapy-morning PEF, evening PEF, asthma symptom scores, rescue albuterol sulfate use, or quality of life. Both active treatments were superior to placebo. However, the salmeterol group had more treatment failures than the triamcinolone group (13/54 [24%] vs 3/54 [6%]; P=.004), as well as more asthma exacerbations (11/54 [20%] vs 4/54 [7%]; P=.04), greater increases in median (interquartile range) sputum eosinophils (2.4% [0.0% to 10.6%] vs -0.1% [-0.7% to 0.3%]; P<.001), eosinophil cationic protein (71 [-2 to 430] U/L vs -4 [-31 to 56] U/L; P=.005), and tryptase (3.1 [2.1 to 7.6] ng/mL vs 0.0 [0.0 to 0.7] ng/mL; P<.001). The duration of benefit when patients were switched from active treatment to placebo after 22 weeks of randomized treatment was not significantly longer in the triamcinolone group than in the salmeterol group. Conclusions: Patients with persistent asthma well controlled by low doses of triamcinolone cannot be switched to salmeterol monotherapy without risk of clinically significant loss of asthma control.

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